Low-frequency material properties of tissues, such as stiffness or mobility, have been shown to be associated with diseases such as atherosclerosis and neoplasms. The long-term goal of this program is to produce methods for measuring and imaging low-frequency material properties of biologic tissues with high resolution and contrast using our novel ultrasound stimulated acoustic emission method. The resulting noninvasive measures of arterial stiffness would be amenable to studies in populations. In the currently proposed program we pursue the goal of detecting and imaging calcified and non-calcified placque within excised arteries, and in animal models, with an imaging technique that uses acoustic emission to map the mechanical response of an object to local cyclic radiation forces produced by interfering ultrasound beams. The novelty of our approach is that the induced motion of tissue is detected by its acoustic emission resulting in a sensitivity to displacement of the order of a few Angstroms. The method, which we call "Ultrasonic Stimulated Acoustic Emission (USAE)", appears well suited to both micro- detection and macro-detection of calcification and less hard tissues. The approach results from ultrasonic radiation pressure stimulation of vibration using dual beam or confocal transducer geometries. This program studies excised human and in vivo swine arteries, with and without disease, comparing USAE images and spectra to histologic analyses of the arteries. Preliminary results clearly delineate calcified, non-calcified, and normal arterial segments in USAE images obtained at acoustic emission frequencies ranging from 7 kHz to 41 kHz. Very early detection of atherosclerosis using a noninvasive instrument such as a modern ultrasound scanner equipped with ultrasonic stimulated acoustic emission, would provide a useful method of delineating non- symptomatic atherosclerosis patients with nascent disease from those without this systemic occult disease. Successful completion of this program will result in USAE methods that are immediately applicable to clinical studies.